Celiac disease (CD) is one of the most common chronic diseases of the digestive system, and is readily treatable with exclusion of dietary gluten. In preliminary studies we found that the prevalence of silent celiac disease is close to 1 % of the US population and 4-10% of those whose family members have CD or type one diabetes mellitus (T1DM). Symptomatic CD can be a devastating illness that is associated with a doubling of mortality and substantial morbidity, and much of this is preventable or reversible with the gluten free diet (GFD). Serological testing can readily detect substantial numbers of individuals with CD in the absence of classical symptoms. However it is not clear if adverse outcomes occur in all patients with CD or just the small part that are clinically obvious. It is of crucial importance to know the long-term outcome of silent and hence untreated, celiac disease. We will test the stored serum of large cohorts of residents from Olmsted County, a medically well studied population to identify those with silent celiac disease. We have established the prevalence of clinically diagnosed CD and the prevalence in their relatives and those with T1DM and anemia in this community. This addresses the hypothesis that undiagnosed celiac disease is common in the generalpopulation today. To test the hypothesis that celiac disease was as prevalent 50 years ago as it is today, the prevalence of CD in 50-year-old serum taken from a large historical military cohort of young adults for whom 45-year outcome data are available will be similarly analyzed. The outcome of both of the military cohort in terms of mortality has been established thereby allowing us to test the hypothesis that undetected celiac disease is ultimately associated with decreased survival over 45 years. Once those with silent CD are identified in Olmsted County we can determine the long-term morbidity of celiac disease, by first examining all diagnoses recorded before and after the sample date for subjects with and without evidence of CD. Secondly we will test disease association by case-control studies. Thirdly, we will determine morbidity of the military cohort using data already abstracted through 1996. The significance of this project for the public health is that it will provide novel comprehensive information on the long-term outcome of silent celiac disease over a long period of time. This will provide crucial data that will determine the need for early detection by screening and treatment of silent celiac disease, which may affect 1% of Americans.